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Differential induction of tumor necrosis factor alpha and manganese superoxide dismutase by endotoxin in human monocytes: role of protein tyrosine kinase, mitogen-activated protein kinase, and nuclear factor kappaB.
J Cell Physiol. 2000 Mar; 182(3):381-9.JC

Abstract

A mutant Escherichia coli lipopolysaccharide (LPS) lacking myristoyl fatty acid markedly stimulates the activity of manganese superoxide dismutase (MnSOD) without inducing tumor necrosis factor alpha (TNFalpha) production by human monocytes (Tian et al., 1998, Am J Physiol 275:C740.), suggesting that induction of MnSOD and TNFalpha by LPS are regulated through different signal transduction pathways. The protein tyrosine kinase (PTK)/mitogen-activated protein kinase (MAPK) pathway plays an important role in the LPS-induced TNFalpha production. In the current study, we determined the effects of PTK inhibitors, genistein and herbimycin A, on the induction of MnSOD and TNFalpha in human monocytes. Genistein (10 microg/ml) and herbimycin A (1 microg/ml) markedly inhibited LPS-induced protein tyrosine phosphorylation, phosphorylation and nuclear translocation of MAPK (p42 ERK, extracellular signal-regulated kinase), and increases in the steady state level of TNFalpha mRNA as well as TNFalpha production. In contrast, at similar concentrations, genistein and herbimycin A had no effect on the LPS-induced activation of nuclear factor kappaB (NFkappaB) and induction of MnSOD (mRNA and enzyme activity) in human monocytes. In addition, inhibition of NFkappaB activation by gliotoxin and pyrrodiline dithiocarbamate, inhibited LPS induction of TNFalpha and MnSOD mRNAs. These results suggest that (1) while PTK and MAPK are essential for the production of TNFalpha, they are not necessary for the induction of MnSOD by LPS, and (2) while activation of NFkappaB alone is insufficient for the induction of TNFalpha mRNA by LPS, it is necessary for the induction of TNFalpha as well as MnSOD mRNAs.

Authors+Show Affiliations

Research Services, Stratton Veterans Administration Medical Center, Albany, New York 12208, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

10653605

Citation

White, J E., et al. "Differential Induction of Tumor Necrosis Factor Alpha and Manganese Superoxide Dismutase By Endotoxin in Human Monocytes: Role of Protein Tyrosine Kinase, Mitogen-activated Protein Kinase, and Nuclear Factor KappaB." Journal of Cellular Physiology, vol. 182, no. 3, 2000, pp. 381-9.
White JE, Lin HY, Davis FB, et al. Differential induction of tumor necrosis factor alpha and manganese superoxide dismutase by endotoxin in human monocytes: role of protein tyrosine kinase, mitogen-activated protein kinase, and nuclear factor kappaB. J Cell Physiol. 2000;182(3):381-9.
White, J. E., Lin, H. Y., Davis, F. B., Davis, P. J., & Tsan, M. F. (2000). Differential induction of tumor necrosis factor alpha and manganese superoxide dismutase by endotoxin in human monocytes: role of protein tyrosine kinase, mitogen-activated protein kinase, and nuclear factor kappaB. Journal of Cellular Physiology, 182(3), 381-9.
White JE, et al. Differential Induction of Tumor Necrosis Factor Alpha and Manganese Superoxide Dismutase By Endotoxin in Human Monocytes: Role of Protein Tyrosine Kinase, Mitogen-activated Protein Kinase, and Nuclear Factor KappaB. J Cell Physiol. 2000;182(3):381-9. PubMed PMID: 10653605.
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TY - JOUR T1 - Differential induction of tumor necrosis factor alpha and manganese superoxide dismutase by endotoxin in human monocytes: role of protein tyrosine kinase, mitogen-activated protein kinase, and nuclear factor kappaB. AU - White,J E, AU - Lin,H Y, AU - Davis,F B, AU - Davis,P J, AU - Tsan,M F, PY - 2000/2/1/pubmed PY - 2000/2/1/medline PY - 2000/2/1/entrez SP - 381 EP - 9 JF - Journal of cellular physiology JO - J Cell Physiol VL - 182 IS - 3 N2 - A mutant Escherichia coli lipopolysaccharide (LPS) lacking myristoyl fatty acid markedly stimulates the activity of manganese superoxide dismutase (MnSOD) without inducing tumor necrosis factor alpha (TNFalpha) production by human monocytes (Tian et al., 1998, Am J Physiol 275:C740.), suggesting that induction of MnSOD and TNFalpha by LPS are regulated through different signal transduction pathways. The protein tyrosine kinase (PTK)/mitogen-activated protein kinase (MAPK) pathway plays an important role in the LPS-induced TNFalpha production. In the current study, we determined the effects of PTK inhibitors, genistein and herbimycin A, on the induction of MnSOD and TNFalpha in human monocytes. Genistein (10 microg/ml) and herbimycin A (1 microg/ml) markedly inhibited LPS-induced protein tyrosine phosphorylation, phosphorylation and nuclear translocation of MAPK (p42 ERK, extracellular signal-regulated kinase), and increases in the steady state level of TNFalpha mRNA as well as TNFalpha production. In contrast, at similar concentrations, genistein and herbimycin A had no effect on the LPS-induced activation of nuclear factor kappaB (NFkappaB) and induction of MnSOD (mRNA and enzyme activity) in human monocytes. In addition, inhibition of NFkappaB activation by gliotoxin and pyrrodiline dithiocarbamate, inhibited LPS induction of TNFalpha and MnSOD mRNAs. These results suggest that (1) while PTK and MAPK are essential for the production of TNFalpha, they are not necessary for the induction of MnSOD by LPS, and (2) while activation of NFkappaB alone is insufficient for the induction of TNFalpha mRNA by LPS, it is necessary for the induction of TNFalpha as well as MnSOD mRNAs. SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/10653605/Differential_induction_of_tumor_necrosis_factor_alpha_and_manganese_superoxide_dismutase_by_endotoxin_in_human_monocytes:_role_of_protein_tyrosine_kinase_mitogen_activated_protein_kinase_and_nuclear_factor_kappaB_ L2 - https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<381::AID-JCP9>3.0.CO;2-F DB - PRIME DP - Unbound Medicine ER -